U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula 2C14H10Cl2NO2.Ca
Molecular Weight 630.3602
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DICLOFENAC CALCIUM

SMILES

c1ccc(c(c1)CC(=O)[O-])Nc2c(cccc2Cl)Cl.c1ccc(c(c1)CC(=O)[O-])Nc2c(cccc2Cl)Cl.[Ca+2]

InChI

InChIKey=LUCXOFIZQAAKNM-UHFFFAOYSA-L
InChI=1S/2C14H11Cl2NO2.Ca/c2*15-10-5-3-6-11(16)14(10)17-12-7-2-1-4-9(12)8-13(18)19;/h2*1-7,17H,8H2,(H,18,19);/q;;+2/p-2

HIDE SMILES / InChI

Molecular Formula Ca
Molecular Weight 40.078
Charge 2
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C14H10Cl2NO2
Molecular Weight 295.1411
Charge -1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/25963327 | https://www.ncbi.nlm.nih.gov/pubmed/20470236 | http://www.pharmaceutical-journal.com/news-and-analysis/news/diclofenac-a-useful-drug-that-may-now-be-entering-its-twilight-years/11121261.article

Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) of the phenylacetic acid class with anti-inflammatory, analgesic, and antipyretic properties. Contrary to the action of many traditional NSAIDs, diclofenac inhibits cyclooxygenase (COX)-2 enzyme with greater potency than it does COX-1. In addition diclofenac can inhibit the thromboxane-prostanoid receptor, affect arachidonic acid release and uptake, inhibit lipoxygenase enzymes, and activate the nitric oxide-cGMP antinociceptive pathway. Other novel mechanisms of action may include the inhibition of substrate P, inhibition of peroxisome proliferator activated receptor gamma (PPARgamma), blockage of acid-sensing ion channels, alteration of interleukin-6 production, and inhibition of N-methyl-D-aspartate (NMDA) receptor hyperalgesia. Similar to other NSAIDs, diclofenac is associated with serious dose-dependent gastrointestinal, cardiovascular, and renal adverse effects. Since its introduction in 1973, a number of different diclofenac-containing drug products have been developed with the goal of improving efficacy, tolerability, and patient convenience. Delayed- and extended-release forms of diclofenac sodium were initially developed with the goal of improving the safety profile of diclofenac and providing convenient, once-daily dosing for the treatment of patients with chronic pain. New drug products consisting of diclofenac potassium salt were associated with faster absorption and rapid onset of pain relief. These include diclofenac potassium immediate-release tablets, diclofenac potassium liquid-filled soft gel capsules, and diclofenac potassium powder for oral solution. The advent of topical formulations of diclofenac enabled local treatment of pain and inflammation while minimizing systemic absorption of diclofenac. SoluMatrix diclofenac, consisting of submicron particles of diclofenac free acid and a proprietary combination of excipients, was developed to provide analgesic efficacy at reduced doses associated with lower systemic absorption. The drug's likely impact on the Asian vulture population was widely reported. The dramatic mortality was attributed largely to renal failure caused by exposure to diclofenac in livestock carcasses on which the birds fed. Although not the most endearing species, vultures are important environmental scavengers and, since veterinary use of diclofenac was stopped in the region in 2006, the decline in vulture numbers has slowed.

Originator

Curator's Comment:: reference retrieved from http://www.pharmaceutical-journal.com/news-and-analysis/news/diclofenac-a-useful-drug-that-may-now-be-entering-its-twilight-years/11121261.article

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
DICLOFENAC SODIUM

Approved Use

Diclofenac Sodium Extended-release Tablets are indicated: •For relief of the signs and symptoms of osteoarthritis •For relief of the signs and symptoms of rheumatoid arthritis
Primary
DICLOFENAC SODIUM

Approved Use

Diclofenac Sodium Extended-release Tablets are indicated: •For relief of the signs and symptoms of osteoarthritis •For relief of the signs and symptoms of rheumatoid arthritis
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
902 ng/mL
50 mg 3 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DICLOFENAC plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
302 ng/mL
12.5 mg 3 times / day steady-state, oral
dose: 12.5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DICLOFENAC plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
749 ng/mL
25 mg 3 times / day steady-state, oral
dose: 25 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DICLOFENAC plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1208 ng × h/mL
50 mg 3 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DICLOFENAC plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
319 ng × h/mL
12.5 mg 3 times / day steady-state, oral
dose: 12.5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DICLOFENAC plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
609 ng × h/mL
25 mg 3 times / day steady-state, oral
dose: 25 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DICLOFENAC plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.64 h
50 mg 3 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DICLOFENAC plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1.19 h
12.5 mg 3 times / day steady-state, oral
dose: 12.5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DICLOFENAC plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1.87 h
25 mg 3 times / day steady-state, oral
dose: 25 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DICLOFENAC plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
2.3 h
unknown, oral
DICLOFENAC serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
unknown, oral
DICLOFENAC serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
75 mg/mL single, intravenous
Dose: 75 mg/mL
Route: intravenous
Route: single
Dose: 75 mg/mL
Sources:
healthy, 18 - 53 years
Health Status: healthy
Age Group: 18 - 53 years
Sex: M+F
Sources:
50 mg single, oral
Dose: 50 mg
Route: oral
Route: single
Dose: 50 mg
Sources:
healthy, 21-51 years
n = 24
Health Status: healthy
Age Group: 21-51 years
Sex: M+F
Population Size: 24
Sources:
Other AEs: Nephrotoxicity...
Other AEs:
Nephrotoxicity
Sources:
500 mg single, oral
Overdose
Dose: 500 mg
Route: oral
Route: single
Dose: 500 mg
Sources:
unknown, adult
Health Status: unknown
Age Group: adult
Sex: unknown
Sources:
Disc. AE: Drowsiness, Lethargy...
AEs leading to
discontinuation/dose reduction:
Drowsiness
Lethargy
Nausea
Vomiting
Epigastric pain
Sources:
AEs

AEs

AESignificanceDosePopulation
Nephrotoxicity
50 mg single, oral
Dose: 50 mg
Route: oral
Route: single
Dose: 50 mg
Sources:
healthy, 21-51 years
n = 24
Health Status: healthy
Age Group: 21-51 years
Sex: M+F
Population Size: 24
Sources:
Drowsiness Disc. AE
500 mg single, oral
Overdose
Dose: 500 mg
Route: oral
Route: single
Dose: 500 mg
Sources:
unknown, adult
Health Status: unknown
Age Group: adult
Sex: unknown
Sources:
Epigastric pain Disc. AE
500 mg single, oral
Overdose
Dose: 500 mg
Route: oral
Route: single
Dose: 500 mg
Sources:
unknown, adult
Health Status: unknown
Age Group: adult
Sex: unknown
Sources:
Lethargy Disc. AE
500 mg single, oral
Overdose
Dose: 500 mg
Route: oral
Route: single
Dose: 500 mg
Sources:
unknown, adult
Health Status: unknown
Age Group: adult
Sex: unknown
Sources:
Nausea Disc. AE
500 mg single, oral
Overdose
Dose: 500 mg
Route: oral
Route: single
Dose: 500 mg
Sources:
unknown, adult
Health Status: unknown
Age Group: adult
Sex: unknown
Sources:
Vomiting Disc. AE
500 mg single, oral
Overdose
Dose: 500 mg
Route: oral
Route: single
Dose: 500 mg
Sources:
unknown, adult
Health Status: unknown
Age Group: adult
Sex: unknown
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
moderate
no
no
no
no
strong
weak
weak
weak
yes [Ki 11 uM]
yes [Ki 19 uM]
yes [Ki 28 uM]
yes [Ki 52 uM]
yes [Ki 60 uM]
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
minor
minor
minor
moderate
no
no
no
no
no
no
no
no
no
no
no
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
Tox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
Nimesulide, a balanced drug for the treatment of osteoarthritis.
2001
Tolerability profiles of rofecoxib (Vioxx) and Arthrotec. A comparison of six weeks treatment in patients with osteoarthritis.
2001
Celecoxib versus diclofenac in the management of osteoarthritis of the knee.
2001
Review: uveitis and immunosuppressive drugs.
2001 Apr
Cataflam-induced esophageal ulceration.
2001 Apr
Anti-inflammatory drugs. IX. Hydrated diethylammonium (2-(2,6-dichlorophenylamino)phenyl)acetate (HDEA.D.H2O).
2001 Apr
Efficacy of peripheral morphine analgesia in inflamed, non-inflamed and perineural tissue of dental surgery patients.
2001 Apr
Corneal complications associated with topical ophthalmic use of nonsteroidal antiinflammatory drugs.
2001 Apr
Influence of electrical and chemical factors on transdermal iontophoretic delivery of three diclofenac salts.
2001 Apr
The role of matrix metalloproteinases in ulcerative keratolysis associated with perioperative diclofenac use.
2001 Apr
Tramadol vs. diclofenac for posttonsillectomy analgesia.
2001 Apr
Treatment of elderly patients with nabumetone or diclofenac: gastrointestinal safety profile.
2001 Apr
The epithelial flap for photorefractive keratectomy.
2001 Apr
Inhibition of phenytoin hydroxylation in human liver microsomes by several selective serotonin re-uptake inhibitors.
2001 Apr
Equivalence of generic and brand-name ophthalmic products.
2001 Apr 1
HPLC evaluation of diclofenac in transdermal therapeutic preparations.
2001 Apr 17
Oil components modulate physical characteristics and function of the natural oil emulsions as drug or gene delivery system.
2001 Apr 28
Inhibition of COX in ocular tissues: an in vitro model to identify selective COX-2 inhibitors.
2001 Feb
Comparative study of diclofenac sodium and paracetamol for treatment of pain after adenotonsillectomy in children.
2001 Feb
Diclofenac-induced gastric mucosal fluorescence in rats.
2001 Feb
Determination of diclofenac sodium, flufenamic acid, indomethacin and ketoprofen by LC-APCI-MS.
2001 Feb
Bioequivalence of two aceclofenac tablet formulations after a single oral dose to healthy male Korean volunteers.
2001 Feb
When should diclofenac be given in ambulatory surgery: preoperatively or postoperatively?
2001 Feb
[Concentrations of diclofenac in aqueous humor and in plasma after i.v. injection in 59 patients undergoing cataract surgery--a prospective study].
2001 Feb
Minocycline inhibits the production of inducible nitric oxide synthase in articular chondrocytes.
2001 Feb
[Topical administration is better than oral administration].
2001 Feb 1
Determination of drug residues in water by the combination of liquid chromatography or capillary electrophoresis with electrospray mass spectrometry.
2001 Feb 23
A comparative experimental study of the effects of diclofenac and ketoprofen on the small-bowel mucosa of canines.
2001 Jan
Using evidence from different sources: an example using paracetamol 1000 mg plus codeine 60 mg.
2001 Jan 10
[Liver damage and nonsteroidal anti-inflammatory drugs: case non-case study in the French Pharmacovigilance Database].
2001 Jan-Feb
Is diclofenac a valuable CYP2C9 probe in humans?
2001 Jan-Feb
Analgesic effect of epidural neostigmine after abdominal hysterectomy.
2001 Mar
Perioperative intravenous flurbiprofen reduces postoperative pain after abdominal hysterectomy.
2001 Mar
Docetaxel extravasation.
2001 Mar
[Effect of tobramycin with topical diclofenac on arachidonic acid in endotoxin-induced uveitis].
2001 Mar
Age-related changes in skin permeability of hydrophilic and lipophilic compounds in rats.
2001 Mar
An assessment of the clinical efficacy of intranasal desmopressin spray in the treatment of renal colic.
2001 Mar
Physical incompatibility between atracurium and intravenous diclofenac.
2001 Mar
Role of the epithelium in opposing H(2)O(2)-induced modulation of acetylcholine-induced contractions in rabbit intrapulmonary bronchiole.
2001 Mar
Pharmacokinetics of oral diclofenac and acetaminophen in children after surgery.
2001 Mar
Cytochrome P450 expression and related metabolism in human buccal mucosa.
2001 Mar
Enhanced disruption of the blood-aqueous barrier and the incidence of angiographic cystoid macular edema by topical timolol and its preservative in early postoperative pseudophakia.
2001 Mar
Simultaneous quantification of neutral and acidic pharmaceuticals and pesticides at the low-ng/l level in surface and waste water.
2001 Mar 16
Use of ion-exchange resins to prepare 100 microm-sized microcapsules with prolonged drug-release by the Wurster process.
2001 Mar 23
Decreased flow-dependent dilation in carotid arteries of tissue kallikrein-knockout mice.
2001 Mar 30
Keratitis, ulceration, and perforation associated with topical nonsteroidal anti-inflammatory drugs.
2001 May
Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney.
2001 May
Structure-hepatic disposition relationships for cationic drugs in isolated perfused rat livers: transmembrane exchange and cytoplasmic binding process.
2001 May
Characterization of rat and human UDP-glucuronosyltransferases responsible for the in vitro glucuronidation of diclofenac.
2001 May
Diclofenac sodium injection sterilized by autoclave and the occurrence of cyclic reaction producing a small amount of impurity.
2001 May
Patents

Sample Use Guides

For topical dosage form (gel): For actinic keratosis using Solaraze® 3% gel: Adults—Apply to affected skin area two times a day. Children—Use and dose must be determined by your doctor. For osteoarthritis of the hands, elbows, or wrists using Voltaren® 1% gel: Adults—Apply 2 grams to the affected skin areas four times a day (a total of 8 grams each day). However, the total dose should not exceed 32 grams per day over all affected joints. Use the enclosed dosing card to measure the appropriate dose. Children—Use and dose must be determined by your doctor. For osteoarthritis of the knees, ankles, or feet using Voltaren® 1% gel: Adults—Apply 4 grams to the affected skin areas four times a day (a total of 16 grams each day). However, the total dose should not exceed 32 grams per day over all affected joints. Use the enclosed dosing card to measure the appropriate dose. Children—Use and dose must be determined by your doctor. For topical dosage form (solution): For osteoarthritis of the knee: Adults—40 drops (10 drops at a time) on each affected knee four times a day. Children—Use and dose must be determined by your doctor. For transdermal dosage form (skin patch): For acute pain: Adults—One patch applied to the painful area two times a day. Children—Use and dose must be determined by your doctor. For oral dosage form (capsules): For acute pain: Adults—18 or 35 milligrams (mg) three times a day. Children—Use and dose must be determined by your doctor. For osteoarthritis: Adults—35 milligrams (mg) three times a day. Children—Use and dose must be determined by your doctor. For oral dosage forms (delayed-release tablets, enteric-coated tablets): For ankylosing spondylitis: Adults—25 milligrams (mg) four times a day, with an extra 25 mg dose at bedtime if necessary. Children—Use and dose must be determined by your doctor. For osteoarthritis: Adults—50 milligrams (mg) two or three times a day, or 75 mg two times a day. Children—Use and dose must be determined by your doctor. For rheumatoid arthritis: Adults—50 milligrams (mg) three or four times a day, or 75 mg two times a day. Children—Use and dose must be determined by your doctor. For oral dosage form (immediate-release tablets): For osteoarthritis: Adults—50 milligrams (mg) two or three times a day. Children—Use and dose must be determined by your doctor. For pain or menstrual cramps: Adults—50 milligrams (mg) three times a day. Your doctor may direct you to take 100 mg for the first dose only. Children—Use and dose must be determined by your doctor. For rheumatoid arthritis: Adults—50 milligrams (mg) three or four times a day. Children—Use and dose must be determined by your doctor. For oral dosage form (solution): For migraine headaches: Adults—One packet (50 milligrams) as a single, one time dose. Children—Use and dose must be determined by your doctor.
Route of Administration: Other
Acute (24 h) diclofenac toxicity in a range of (10-1000 μM) concentrations was assesed in primary human hepatocytes. The chronic (9 repeated doses) toxicity at one clinically relevant and another higher concentration (6.4 and 100 μM) was also tested. Acute 24 h assessment revealed toxicity only for the highest tested concentration (1 mM). Upon repeated dose exposure, toxic effects were observed even at a low, clinically relevant concentration (6.4 μM).
Substance Class Chemical
Created
by admin
on Sat Jun 26 08:37:35 UTC 2021
Edited
by admin
on Sat Jun 26 08:37:35 UTC 2021
Record UNII
PU75M58TSF
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DICLOFENAC CALCIUM
Common Name English
BENZENEACETIC ACID, 2-((2,6-DICHLOROPHENYL)AMINO)-, CALCIUM SALT (2:1)
Systematic Name English
CALCIUM DICLOFENAC
Common Name English
DICLOFENAC CALCIUM SALT
Common Name English
Code System Code Type Description
CAS
88170-10-9
Created by admin on Sat Jun 26 08:37:35 UTC 2021 , Edited by admin on Sat Jun 26 08:37:35 UTC 2021
PRIMARY
PUBCHEM
13239661
Created by admin on Sat Jun 26 08:37:35 UTC 2021 , Edited by admin on Sat Jun 26 08:37:35 UTC 2021
PRIMARY
EPA CompTox
88170-10-9
Created by admin on Sat Jun 26 08:37:35 UTC 2021 , Edited by admin on Sat Jun 26 08:37:35 UTC 2021
PRIMARY
FDA UNII
PU75M58TSF
Created by admin on Sat Jun 26 08:37:35 UTC 2021 , Edited by admin on Sat Jun 26 08:37:35 UTC 2021
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY